Two Things About COVID-19 Might Need Attention

The spread of 2019 novel coronavirus disease (COVID-19) throughout the world has been a severe challenge for public health. The human angiotensin-converting enzyme 2 (ACE2) has a remarkably high affinity binding to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). By the search for network database and re-analysis of pubic data, we found the level of ACE2 expression in adipose tissue was higher than that in lung tissue, which indicated the Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 23 February 2020 © 2020 by the author(s). Distributed under a Creative Commons CC BY license. doi:10.20944/preprints202002.0315.v1

adipose tissue might be vulnerable to SARS-CoV-2 as well; the levels of ACE2 expressed by adipocytes and adipose progenitor cells were similar between non-obese individuals and obese individuals, but obese individuals have more adiposes so as to increase the number of ACE2expressing cells; the expression of ACE2 in tumor tissues posed by five different types of cancers increased significantly compared with that in adjacent tissues. Thus, we suggest that more attentions might be given to obese individuals and the five types of cancer patients during the outbreak of COVID-19.

Instruction
The COVID-19 that outbroke in Wuhan (Hubei province, China) in 2019 has become a public health emergency of international concern, and it was caused by the SARS-CoV-2 1 . As of 11:00 on February 21, 2020, there are 75,567 confirmed cases, 5,206 suspected cases, and 2,239 death cases in China.
The spike protein 3-D structure of SARS-CoV-2 is similar to that of SARS-CoV, and hence SARS-CoV-2 is also feasible to bind to ACE2 2 . The binding affinity between ACE2 and SARS-CoV-2 is approximately 10-to 20-fold higher than that between ACE2 and SARS-CoV 3 .
Therefore, those ACE2-expressing cells and tissues, potentially act as targets of the novel coronavirus 4 .
Two things in our research were explored to suppose some suggestions for prevention and treatment of COVID-19. First, is adipose potentially infected by SARS-CoV-2? It is reported that adipose tissues could be infected by some virus, like H5N1, HIV 5,6 . Furthermore, obesity could influence the mortality and transmission of influenza virus 7,8 . To date, no research has demonstrated that SARS-CoV-2 could infect adipose tissue. Moreover, there is still no evidence to show that obesity is associated with COVID-19. Second, although the COVID-19 patients with cancers have higher severe events 9 , is the risk of different types of cancer patients facing with SARS-CoV-2 similar?

Cell ACE2 expression analysis
The cohort of obese and non-obese individuals was derived from public datasets (GEO: GSE80654), including RNA expression profiling by microarray of major white adipose tissue cell types (adipocytes from 7 non-obese and 7 obese human adipose tissue, progenitor cells from 10 non-obese and 9 obese human adipose tissue). Gene expression data was extracted and analyzed in R 3.4.4 statistical software.

One: Adipose tissue might be infected by SARS-Cov-2.
We have employed two databases, HCCDB and HPA, to search the SARS-Cov-2 receptor ACE2 in normal tissues. In terms of RNA level, it shows that the expression of ACE2 in heart, kidney, testis, intestine and bladder is higher than that in lung, which is consistent with the previous report by Zin Zhou et al 4 . Moreover, we found the expression of ACE2 in gallbladder and adipose tissue (including subcutaneous and visceral) is significantly higher than that in lung ( Figure 1). In addition, we have explored whether obesity could affect the expression of ACE2.
On account of data deficiency, it is impossible to test ACE2 expression in the whole adipose tissue. Nevertheless, the level of ACE2 expression in adipocytes and adipocyte progenitor cells isolated from adipose tissues of non-obese and obese individuals was compared by re-analysis of public data from Anna Ehrlund et al 15 (Figure 3). The expression level of ACE2 in tumor tissue of CESC was closed to that in lung tissue, whereas the expression level of ACE2 in tumor tissue of PAAD got higher than that in lung tissue. In conclusion, the risk that these cancer sites infected by SARS-Cov-2 might increase.

Discussion
Some organs (kidney, liver, bladder, testis et al.) were demonstrated to have the potential risk of SARS-Cov-2 infection by characterizing the expression patterns of ACE2 16,17 . However, it has not been reported whether the adipose tissue might be vulnerable to the novel virus. We used the public database to analyze the ACE2 expression in adipose tissue, and found a higher RNA level than lung tissue. It was reported that adipose tissue could serve as a reservoir for human adenovirus Ad-36, influenza A virus, HIV, cytomegalovirus Trypanosoma gondii, and Mycobacterium tuberculosis 18 . Certainly, it's further required to be determined whether SARS-Cov-2 could infect adipose tissue through nucleic acid detection and pathological diagnosis for adipose tissue.  20,21 . Obesity was reported to increase vulnerability to infection 22 . Obesity is an independent risk factor for hospitalization and death to H1N1 influenza virus, and HFD-induced and genetic-induced obese mice exhibited greater H1N1 mortality 7 . Symptomatic obese adults were shown to shed influenza A virus 42% longer than non-obese adults. Obesity increases the duration of influenza A virus shedding in adults, which suggests obesity may play an important role in influenza transmission 8 . Even though obesity really has no effect on ACE2 expression, the obese individuals have more adipose to increase the quantities of ACE2 proteins. Therefore, the role of obesity in SARS-Cov-2 infection shouldn't be ignored. Wenhua Liang et al. analyzed the risk for COVID-19 in patients with cancer for the first time, and they found cancer patients had more severe events 9 . As limited number of COVID-19 patients with cancer, they couldn't compare the severe events between different types of cancers. We found five types of cancers (CESC, PAAD, READ, KIRP and KIRC) increased the ACE2 expression at the original organs, which might worsen the COVID-19. It's also required more clinical data to further verify this find.
Finally, we proposed two suggestions at this critical period of epidemic. First, the above cancer patients and obese individuals should pay great attention to protection from SARS-Cov-2 infection. Second, the more intensive surveillance or treatment should be delivered to the above cancer patients and obese individuals in the early stages of COVID-19.